一氧化氮在实验性大鼠脑动脉瘤形成中的作用

目的观察一氧化氮合酶（iNOS）在实验性脑动脉瘤组织局部的表达情况和选择性iNOS抑制剂氨基胍对动脉瘤发生和血清一氧化氮（NO）水平的影响。方法50只SD大鼠随机分为3组，结扎左侧颈总动脉和双侧肾动脉后支建立脑动脉瘤模型。A组给予氨基胍干预；B组给予生理盐水；C组为阴性对照。5个月后灌注固定取右侧大脑前动脉／嗅动脉（ACA／OA）分叉部标本和动物血清，用HE染色评价动脉瘤的发生率和病理特征，免疫组化评价动脉瘤组织iNOS的局部表达特点，并测量血清硝酸盐含量。结果氨基胍可明显抑制动脉瘤的发生和血清硝酸盐水平。诱导的动脉瘤病理特征和外形与人动脉瘤组织相似，主要表现为内弹力膜断裂或消失，平滑肌细胞层变薄和消失，动脉瘤壁代之以一层纤维结缔组织。在动脉瘤样改变的内膜垫和颈部远侧可见散在的iNOS染色阳性平滑肌细胞。结论动脉瘤的发生与局部增高的NO有关。

The role of nitric oxide in the formation of experimental cerebral aneurysms in rats

Objective To investigate the iNOS expression in cerebral aneurysm tissue, and the effect of selective iNOS inhibitor aminoguanidine on experimental cerebral aneurysm formation and serum NO production. Methods Fifty SD rats were divided into 3 groups randomly. To reproduce the aneurysm model, 40 adult male rats (weight, 250-300g) were subjected to ligation of the left common carotid artery and the posterior branches of both renal arteries. One week after the operation, 1% saline was given for drinking to substitute plain water. Each rat received an intraperitoneal injection of aminoguanidine (100mg/kg)(group A, n=20) or normal saline (group B, n=20) beginning in the morning of postoperative day(POD) 1 through POD 150. Group C rats received no operation to serve as the control group (n=10). Arterial wall at the bifurcation of the right anterior cerebral artery and olfactory artery as well, as serum were harvested after 5 months. Blood pressure was measured before the experiment and 5 months after the experiment procedure. NO levels were indirectly quantified by measuring nitrate levels. The incidence of formation of aneurysm, pathological findings and expression of iNOS in aneurysmal wall were evaluated with HE staining and immunohistochemical analysis. Results Selective iNOS inhibitor aminoguanidine could significantly inhibit the formation of aneurysms and lower serum levels of nitrate. The pathological features of the experimental aneurysms were similar to that in human, including discontinuation or disappearance of tunica intima, thinning or disappearance of the elastic and muscular layers, and substitution of artery wall by a layer of fibrous connective tissue. iNOS immunoreactivity could be seen in the smooth muscle cells of the intimal pad and distal portion of the newly formed aneurysm. Conclusion Cerebral aneurysm can be induced in rats by alteration in hemodynamics, and it is related to formation of local expression of iNOS and high NO level.